Opioids, e.g., morphine, act in both central and peripheral nervous systems to produce various pharmacological effects including, among others, analgesia and decreased gastrointestinal motility. Opioids have long been used as the most effective analgesics for treating acute pain, e.g., post-operative pain, and chronic pain, e.g., pain from cancer.
Opioids primarily activate three classic subtypes of opioid receptors, which are all G-protein-coupled receptors, namely, mu-opioid receptor (MOR), delta-opioid receptor (DOR), and kappa-opioid receptor (KOR). Currently, most opioids clinically used as analgesics are either nonselective or selective MOR agonists, producing undesired effects, such as respiratory depression. Furthermore, long-term use of these opioids for controlling chronic pain develops severe side effects such as tolerance, dependence, and addiction.
There is a need to develop new MOR modulators that have fewer side effects for the treatment of pain.